Ovarian CancerPhase 1/2ETCNCT00005612
Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Ovarian Epithelial Cancer
A Phase 1/2 study testing filgrastim, carboplatin and cyclophosphamide in people with Ovarian Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- filgrastim, carboplatin and cyclophosphamide
- Type of treatment
- Surgery or procedure
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 1999to Feb 2004
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS: Histologically proven stage IIIC ovarian epithelial cancer Chemosensitive to 6-8 courses of standard dose adjuvant chemotherapy (one regimen), such as cisplatin or carboplatin in combination with paclitaxel, or any other standard dose regimen Residual disease (no greater than 1 cm) following second look laparotomy Ineligible if no microscopic disease present following induction chemotherapy OR Histologically proven newly diagnosed stage IV ovarian epithelial cancer Achieved at least partial response (PR) (80% or greater reduction in tumor by CT scan) following six courses of standard dose chemotherapy (one regimen) OR Residual disease (no greater than 1 cm) or no disease determined at the time of second look laparotomy OR Histologically proven relapsed ovarian epithelial cancer Relapse following standard dose chemotherapy Chemosensitive Achieved at least PR after 4-6 courses of salvage chemotherapy (total of 2 regimens) No more than a six week interval between completion of standard dose chemotherapy and second look laparotomy
PATIENT CHARACTERISTICS: Age: 18 to 65 Performance status: ECOG 0 or 1 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL ALT or AST no greater than 2.5 times normal Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: Ejection fraction at least 50% by MUGA scan No severe cardiac dysfunction or major heart disease No angina pectoris No ventricular dysrhythmias Essential hypertension allowed if controlled with medication(s) Pulmonary: DLCO at least 50% predicted No symptomatic obstructive or restrictive pulmonary disease Other: No active infections HIV negative No uncontrolled insulin dependent diabetes mellitus No uncompensated major thyroid or adrenal dysfunction No other malignancy within the past 5 years except nonmelanomatous skin cancer Not pregnant or nursing Negative pregnancy test
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No prior topotecan Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: See Disease Characteristics Other: No concurrent nitroglycerin preparations or antiarrhythmic drugs
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Phase I/II Study of Intensive-Dose Etoposide, Topotecan and Carboplatin (ETC) Followed by Autologous Stem Cell Rescue in Chemosensitive Ovarian Cancer Patients With Either Minimal Residual Disease or at First Relapse
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy followed by peripheral stem cell transplantation in treating patients who have ovarian epithelial cancer.
Read the detailed description
OBJECTIVES: I. Determine the toxicity and potential efficacy of high dose chemotherapy (HDC) comprised of etoposide, topotecan, and carboplatin (ETC) followed by autologous stem cell transplantation in patients with ovarian epithelial cancer. II. Determine the maximum tolerated dose of topotecan when combined with etoposide and carboplatin in these patients. III. Determine the disease free survival (DFS) and overall survival (OS) in patients treated with this regimen. IV. Measure the amount and subcellular location of DNA topoisomerase I and II- alpha in ovarian cancer biopsies before HDC and at relapse to determine the role of alterations of topoisomerases in the drug resistance of ovarian cancer. V. Correlate the amount and location of both enzymes before HDC with clinical outcome (DFS and OS) and plasma concentrations of topotecan and carboplatin in these patients. VI. Correlate the levels of signal transducers and activators of transcription (STAT) and expression of bcl-2 family proteins with response to chemotherapy and clinical outcome (DFS and OS) in these patients. VII. Measure the levels of STAT and determine the expression of bcl-2 family proteins in tumor biopsies before HDC and at relapse to determine the role of these cellular pathways in drug response. VIII. Determine the pharmacokinetic and pharmacodynamic relationship of high dose topotecan combined with carboplatin in these patients.
OUTLINE: This is a dose escalation study of topotecan. Mobilization: After completion of salvage chemotherapy and within 6 weeks of second look laparotomy, patients receive cyclophosphamide IV over 2 hours and paclitaxel IV over 2 hours for 2 days. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after completion of chemotherapy and continuing until autologous peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells. High dose chemotherapy: After priming chemotherapy and within 6 weeks of second look laparotomy, patients receive carboplatin IV over 1 hour on days -8 to -6; topotecan IV over 30 minutes on days -7 to -5 (beginning 12 hours after completion of carboplatin infusion); and etoposide IV over 4 hours on days -5 to -3 (beginning 12 hours after completion of the last topotecan infusion). Cohorts of 4-12 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 6 or more of 12 patients experience dose limiting toxicity. Transplantation: PBSC are reinfused on day 0. Patients are followed at 3 and 6 months, then annually thereafter.
PROJECTED ACCRUAL: Approximately 4-30 patients will be accrued for this study within 3-4 years.
- Conditions
- Ovarian Cancer
- Being tested
- filgrastim, carboplatin, cyclophosphamide, etoposide, paclitaxel
- Keywords
- stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, recurrent ovarian epithelial cancer
- Medical subject headings
- Ovarian Neoplasms, Carcinoma, Ovarian Epithelial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
carboplatinDrug
cyclophosphamideDrug
etoposideDrug
paclitaxelDrug
topotecan hydrochlorideDrug
peripheral blood stem cell transplantationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Progression free survival is defined as the time from date of enrollment to the time of recurrence
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2004 (estimated)
- Study startAug 1999
- Primary completionFeb 2004
- Study completionFeb 2004
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Karen K. Fields, MD, Study chair, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005612
- Sponsor's protocol ID
- MCC-12085
- Other IDs
- MCC-IRB-5418, NCI-G00-1745
- Acronym
- ETC
- Status last verified
- Sep 2012
- First submitted
- 2 May 2000
- Last updated
- 26 Sep 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Intensive-Dose Etoposide, Topotecan and Carboplatin (ETC) Followed by Autologous Stem Cell Rescue in Chemosensitive Ovarian Cancer Patients With Either Minimal Residual Disease or at First Relapse
- ClinicalTrials.gov ID
- NCT00005612
- Acronym / sponsor ID
- ETC / MCC-12085
- Conditions
- Ovarian Cancer
- Keywords
- stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, recurrent ovarian epithelial cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Aug 1999
- Primary completion
- Feb 2004 (actual)
- Study completion
- Feb 2004 (actual)
- First posted
- 3 May 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy followed by peripheral stem cell transplantation in treating patients who have ovarian epithelial cancer.
Detailed description
OBJECTIVES: I. Determine the toxicity and potential efficacy of high dose chemotherapy (HDC) comprised of etoposide, topotecan, and carboplatin (ETC) followed by autologous stem cell transplantation in patients with ovarian epithelial cancer. II. Determine the maximum tolerated dose of topotecan when combined with etoposide and carboplatin in these patients. III. Determine the disease free survival (DFS) and overall survival (OS) in patients treated with this regimen. IV. Measure the amount and subcellular location of DNA topoisomerase I and II- alpha in ovarian cancer biopsies before HDC and at relapse to determine the role of alterations of topoisomerases in the drug resistance of ovarian cancer. V. Correlate the amount and location of both enzymes before HDC with clinical outcome (DFS and OS) and plasma concentrations of topotecan and carboplatin in these patients. VI. Correlate the levels of signal transducers and activators of transcription (STAT) and expression of bcl-2 family proteins with response to chemotherapy and clinical outcome (DFS and OS) in these patients. VII. Measure the levels of STAT and determine the expression of bcl-2 family proteins in tumor biopsies before HDC and at relapse to determine the role of these cellular pathways in drug response. VIII. Determine the pharmacokinetic and pharmacodynamic relationship of high dose topotecan combined with carboplatin in these patients.
OUTLINE: This is a dose escalation study of topotecan. Mobilization: After completion of salvage chemotherapy and within 6 weeks of second look laparotomy, patients receive cyclophosphamide IV over 2 hours and paclitaxel IV over 2 hours for 2 days. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after completion of chemotherapy and continuing until autologous peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells. High dose chemotherapy: After priming chemotherapy and within 6 weeks of second look laparotomy, patients receive carboplatin IV over 1 hour on days -8 to -6; topotecan IV over 30 minutes on days -7 to -5 (beginning 12 hours after completion of carboplatin infusion); and etoposide IV over 4 hours on days -5 to -3 (beginning 12 hours after completion of the last topotecan infusion). Cohorts of 4-12 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 6 or more of 12 patients experience dose limiting toxicity. Transplantation: PBSC are reinfused on day 0. Patients are followed at 3 and 6 months, then annually thereafter.
PROJECTED ACCRUAL: Approximately 4-30 patients will be accrued for this study within 3-4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| filgrastim | Biological | – |
| carboplatin | Drug | – |
| cyclophosphamide | Drug | – |
| etoposide | Drug | – |
| paclitaxel | Drug | – |
| topotecan hydrochloride | Drug | – |
| peripheral blood stem cell transplantation | Procedure or surgery | – |
Primary outcome
Progression free survival
Time frame: 5 years
Progression free survival is defined as the time from date of enrollment to the time of recurrence
Results and safety
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karen K. Fields, MD study chair
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing filgrastim, carboplatin and cyclophosphamide in people with Ovarian Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2012.